Blood collection systems and methods that derive estimated effects upon the donor&#39;s blood volume and hematocrit

ABSTRACT

Blood processing systems and methods convey blood drawn from a donor through a blood processing circuit to separate the blood into at least one targeted blood component for collection. The systems and methods derive an estimated effect of the procedure upon the donor. The estimated effect can be expressed in terms of a net blood fluid volume loss, or as a hematocrit of the donor after completion of the desired blood collection procedure. The systems and methods present the estimated effect to an operator for viewing, reading, or offloading.

RELATED APPLICATIONS

[0001] This application is a divisional of copending patent applicationSer. No. 09/789,183 filed 20 Feb. 2001, which is a continuation-in-partof application Ser. No. 09/419,742, filed Oct. 16, 1999, and entitled“Automated Collection Systems and Methods for Obtaining Red Blood Cells,Platelets, And Plasma From Whole Blood,” which is incorporated herein byreference.

FIELD OF THE INVENTION

[0002] The invention relates to centrifugal blood processing systems andapparatus.

BACKGROUND OF INVENTION

[0003] Certain therapies transfuse large volumes of blood components.For example, some patients undergoing chemotherapy require thetransfusion of large numbers of platelets on a routine basis. Manualblood bag systems simply are not an efficient way to collect these largenumbers of platelets from individual donors.

[0004] On line blood separation systems are today used to collect largenumbers of platelets to meet this demand. On line systems perform theseparation steps necessary to separate concentration of platelets fromwhole blood in a sequential process with the donor present. On linesystems establish a flow of whole blood from the donor, separate out thedesired platelets from the flow, and return the remaining red bloodcells and plasma to the donor, all in a sequential flow loop.

[0005] Large volumes of whole blood (for example, 2.0 liters) can beprocessed using an on line system. Due to the large processing volumes,large yields of concentrated platelets (for example, 4×10¹¹ plateletssuspended in 200 ml of fluid) can be collected.

[0006] Nevertheless, a need still exists to further improve systems andmethods for collecting cellular-rich concentrates, like red blood cells,from blood components, in a way that lends itself to use in high volume,on line blood collection environments, where higher yields of criticallyneeded cellular blood components like platelets and red blood cells canbe realized.

SUMMARY OF THE INVENTION

[0007] The invention provides blood processing systems and methods thatseparate blood drawn from a donor through a blood processing circuit toperform a desired blood collection procedure. During the procedure, avolume of the targeted blood component is collected. The systems andmethods derive an estimated effect of the procedure upon the donor. Thesystems and methods present the estimated effect to an operator.

[0008] According to one aspect of the invention, the estimated effect isexpressed in terms of a net blood fluid volume loss. In one embodiment,the estimated effect takes into account blood loss due to the volume oftargeted blood component collected and a residual fluid volume of theblood processing circuit. In one embodiment, a volume of replacementfluid is conveyed to the donor during the desired blood collectionprocedure, and the estimated effect takes into account the volume ofreplacement fluid conveyed to the donor. In one embodiment, theestimated effect expresses the net blood fluid volume loss as apercentage of a blood volume of the donor that existed prior to thedesired blood processing procedure. In one embodiment, the estimatedeffect expresses the net blood fluid volume loss as a percentage ofweight of the donor.

[0009] According to another aspect of the invention, the estimatedeffect is expressed in terms of a hematocrit of the donor aftercompletion of the desired blood collection procedure.

[0010] According to either aspect of the invention, blood can beconveyed through the blood processing circuit to collect a volume of redblood cells, or a volume of platelets, a volume of plasma, orcombinations thereof. In one embodiment, in a first mode, platelets arecollected while returning red blood cells to the donor and, in a secondmode, platelets and red blood cells are collected without returningplatelets or red blood cells to the donor.

[0011] According to either aspect of the invention, the estimated effectcan be presented in a visual display, or in printed form, or in a dataform suitable for offloading, or combinations thereof.

[0012] The invention may be embodied in several forms without departingfrom its spirit or essential characteristics. The scope of the inventionis defined in the appended claims, rather than in the specificdescription preceding them. All embodiments that fall within the meaningand range of equivalency of the claims are therefore intended to beembraced by the claims. The invention is not limited to the details ofthe construction and the arrangements of parts set forth in thefollowing description or shown in the drawings. The invention can bepracticed in other embodiments and in various other ways. Theterminology and phrases are used for description and should not beregarded as limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

[0013]FIG. 1 is a diagrammatic view of an on-line blood processingsystem;

[0014]FIG. 2 is a schematic view of a controller that governs theoperation of the blood processing system shown in FIG. 1;

[0015]FIG. 3 is a diagrammatic view of the blood processing system shownin FIG. 1 conditioned by the controller to perform a draw cycle during anon-concurrent collection mode;

[0016]FIG. 4 is a diagrammatic view of the blood processing system shownin FIG. 1 conditioned by the controller to perform a return cycle duringa non-concurrent collection mode;

[0017]FIG. 5 is a diagrammatic view of the blood processing system shownin FIG. 1 conditioned by the controller to perform a concurrentcollection mode;

[0018]FIG. 6 is a diagrammatic view of the blood processing system shownin FIG. 1 conditioned by the controller to perform a blood volumetrimming function; and

[0019]FIG. 7 is a front view of a blood collection set, which, in use,receives red blood cells after collection in the system shown in FIG. 1for further processing prior to storage.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020]FIG. 1 shows in diagrammatic form an on line blood processingsystem 10 for carrying out an automated blood collection procedure.

[0021] As illustrated, the system 10 comprises a single needle bloodcollection network, although a double needle network could also be used.

I. System Overview

[0022] The system 10 includes an arrangement of durable hardwareelements, whose operation is governed by a processing controller 18. Thehardware elements include a centrifuge 12, in which whole blood (WB)from a donor is separated into platelets, plasma, and red blood cells. Arepresentative centrifuge that can be used is shown in Brown et al U.S.Pat. No. 5,690,602, which is incorporated herein by reference.

[0023] The hardware elements will also include various pumps, which aretypically peristaltic (designated P1 to P7); and various in line clampsand valves (designated V1 to V7). Of course, other types of hardwareelements may typically be present, which FIG. 1 does not show, likesolenoids, pressure monitors, and the like.

[0024] The system 10 typically also includes some form of a disposablefluid processing assembly 14 used in association with the hardwareelements. In the illustrated embodiment, the assembly 14 includes aprocessing chamber 16 having two stages 24 and 32. In use, thecentrifuge 12 rotates the processing chamber 16 to centrifugallyseparate blood components.

[0025] The construction of the two stage processing chamber 16 can vary.For example, it can take the form of double bags, like the processingchambers shown and described in Cullis et al. U.S. Pat. No. 4,146,172,which is incorporated herein by reference. Alternatively, the processingchamber 16 can take the form of an elongated two stage integral bag,like that shown and described in Brown U.S. Pat. No. 5,632,893, which isalso incorporated herein by reference.

[0026] In the illustrated blood processing system 10, the processingassembly 14 also includes an array of flexible tubing that forms a fluidcircuit. The fluid circuit conveys liquids to and from the processingchamber 16. The pumps P1-P7 and the valves V1-V7 engage the tubing togovern the fluid flow in prescribed ways. The fluid circuit furtherincludes a number of containers (designated C1 to C5) to dispense andreceive liquids during processing.

[0027] A controller 18 governs the operation of the various hardwareelements to carry out one or more processing tasks using the assembly14. The controller 18 also performs real time evaluation of processingconditions and outputs information to aid the operator in maximizing theseparation and collection of blood components.

[0028] The system 10 can be configured to accomplish diverse types ofblood separation processes. FIG. 1 shows the system 10 configured tocarry out an automated procedure using a single needle 22 to collectfrom a single donor (i) a desired yield of concentrated plateletssuspended in plasma (PC)(e.g., upwards to two therapeutic units), which(if desired) can be provided essentially free of leukocytes, (ii) adesired volume of concentrated red blood cells (RBC) (e.g., upwards toabout 200 ml at a hematocrit of about 100% or upwards to about 230 ml ata hematocrit of about 85%), which (if desired) can also be providedessentially free of leukocytes, and (iii) a desired volume (if desired)of platelet-poor plasma (PPP).

[0029] The system 10 can collect various volumes of PC, PPP, and RBCproducts as governed by applicable regulations for allowable bloodvolumes. For example, in the United States, component volume iterationsthat the system 10 can presently provide include, e.g.:(i) onetherapeutic unit each of PC, PPP, and RBC, or (ii) one therapeutic uniteach of PC and RBC, or (iii) two therapeutic units of PC and one unit ofRBC.

[0030] Further details of the operation of the system 10 to achievethese blood processing objectives will be described later.

II. The System Controller

[0031] The controller 18 carries out the overall process control andmonitoring functions for the system 10 as just described.

[0032] In the illustrated and preferred embodiment (see FIG. 2), thecontroller comprises a main processing unit (MPU) 44. In the preferredembodiment, the MPU 44 comprises a type 68030 microprocessor made byMotorola Corporation, although other types of conventionalmicroprocessors can be used.

[0033] In the preferred embodiment, the MPU 44 employs conventional realtime multi-tasking to allocate MPU cycles to processing tasks. Aperiodic timer interrupt (for example, every 5 milliseconds) preemptsthe executing task and schedules another that is in a ready state forexecution. If a reschedule is requested, the highest priority task inthe ready state is scheduled. Otherwise, the next task on the list inthe ready state is schedule.

[0034] A. Hardware Control

[0035] The MPU 44 includes an application control manager 46. Theapplication control manager 46 administers the activation of a library48 of control applications. Each control application prescribesprocedures for carrying out given functional tasks using the systemhardware (e.g., the centrifuge 12, the pumps P1-P7, and the valvesV1-V7) in a predetermined way. In the illustrated and preferredembodiment, the applications reside as process software in EPROM's inthe MPU 44.

[0036] An instrument manager 50 also resides as process software inEPROM's in the MPU 44. The instrument manager 50 communicates with theapplication control manager 46. The instrument manager 50 alsocommunicates with low level peripheral controllers 52 for the pumps,solenoids, valves, and other functional hardware of the system.

[0037] As FIG. 2 shows, the application control manager 46 sendsspecified function commands to the instrument manager 50, as called upby the activated application. The instrument manager 50 identifies theperipheral controller or controllers 52 for performing the function andcompiles hardware-specific commands. The peripheral controllers 52communicate directly with the hardware to implement thehardware-specific commands, causing the hardware to operate in aspecified way. A communication manager 54 manages low-level protocol andcommunications between the instrument manager 50 and the peripheralcontrollers 52.

[0038] As FIG. 2 also shows, the instrument manager 50 also conveys backto the application control manager 46 status data about the operationaland functional conditions of the processing procedure. The status datais expressed in terms of, for example, fluid flow rates, sensedpressures, and fluid volumes measured.

[0039] The application control manager 46 transmits selected status datafor display to the operator. The application control manager 46transmits operational and functional conditions to the procedureapplication A1 and the performance monitoring application A2.

[0040] B. Operator Interface In the illustrated embodiment, the MPU 44also includes an interactive user interface 58. The interface 58 allowsthe operator to view and comprehend information regarding the operationof the system 10. The interface 58 also allows the operator to selectapplications residing in the application control manager 46, as well asto change certain functions and performance criteria of the system 10.The interface 58 includes an interface screen 60 and, preferably, anaudio device 62. The interface screen 60 displays information forviewing by the operator in alpha-numeric format and as graphical images.The audio device 62 provides audible prompts either to gain theoperator's attention or to acknowledge operator actions.

[0041] In the illustrated and preferred embodiment, the interface screen60 also serves as an input device. It receives input from the operatorby conventional touch activation. Alternatively or in combination withtouch activation, a mouse or keyboard could be used as input devices.

[0042] An interface manager 64 communicates with the interface screen 60and audio device 62. The interface manager 64, in turn, communicateswith the application control manager 46. The interface manager 64resides as process software in EPROM's in the MPU 44.

[0043] Further details of the MPU 44 and interface 58 are disclosed inLyle et al. U.S. Pat. No. 5,581,687, which is incorporated herein byreference.

[0044] C. System Control Functions

[0045] In the illustrated embodiment (as FIG. 2 shows), the library 48includes at least one system control application A1. The system controlapplication A1 contains several specialized, yet interrelated utilityfunctions. Of course, the number and type of utility functions can vary.

[0046] In the illustrated embodiment, a utility function F1 derives theplatelet yield (Yld) of the system 10. The utility function F1ascertains both the instantaneous physical condition of the system 10 interms of its separation efficiencies and the instantaneous physiologicalcondition of the donor in terms of the number of circulating plateletsavailable for collection. From these, the utility function F1 derive theinstantaneous yield of platelets continuously over the processingperiod.

[0047] Another utility function F2 relies upon the calculated plateletyield (Yld) and other processing conditions to generate selectedinformational status values and parameters. These values and parametersare displayed on the interface 58 to aid the operator in establishingand maintaining optimal performance conditions. The status values andparameters derived by the utility function F2 can vary. For example, inthe illustrated embodiment, the utility function F2 reports remainingvolumes to be processed, remaining processing times, and the componentcollection volumes and rates.

[0048] Other utility functions generate control variables based uponongoing processing conditions for use by the applications controlmanager 46 to establish and maintain optimal processing conditions. Forexample, one utility function F3 generates control variables to optimizeplatelet separation conditions in the first stage 24. Another utilityfunction F4 generates control variables to control the rate at whichcitrate anticoagulant is returned with the PPP to the donor to avoidpotential citrate toxicity reactions.

[0049] Further details of these and other utility functions can be foundin Brown U.S. Pat. No. 5,676,841, which is incorporated herein byreference. A summary of various utility functions relied upon is foundat the end of the Specification.

III. System Operation

[0050] In the illustrated embodiment, the system 10 is conditioned toachieve at least three processing objectives. The first objective is thecollection of a desired yield of concentrated platelets (PC). The secondobjective is the collection of a desired volume of PPP to serve as astorage medium for the collected PC. The third objective is thecollection of a desired volume of red blood cells (RBC). Otherobjectives may be established, e.g., to collect an additional volume ofPPP for storage.

[0051] To achieve these objectives, the utility function F1 conditionsthe system 10 to collect and process blood in at least three differentoperating modes.

[0052] In the first operating mode, the system 10 is conditioned toprocess whole blood and collect PC and PPP. In the first mode, RBC arenot concurrently collected, but are returned to the donor. PPP in excessof that desired may also be returned to the donor.

[0053] In the second operating mode, the system 10 is conditioned toprocess whole blood and concurrently collect RBC along with theassociated additional volumes of PC and PPP. During the second mode, noblood components are returned to the donor.

[0054] In the third operating mode, the system 10 is conditioned toperform a final blood volume trimming function. During the volumetrimming function, a portion of the collected RBC volume, or all or someof the collected PPP volume, or both, can be returned to the donor. Thevolume trimming function assures that component volumes actuallycollected do not exceed the volumes targeted for collection.

[0055] At the outset of the processing procedure, the operator uses theinterface 58 to input the desired PC yield to be collected (Yld_(Goal)),the desired RBC volume to be collected(RBC_(Goal)), and the desired PPPvolume to be collected (PPP_(Goal)).

[0056] The controller 18 conditions the system 10 to proceed with bloodprocessing in the first operating mode. The controller 18 takes intoaccount two processing variables in commanding a change from the firstoperating mode to the second operating mode, and from the secondoperating mode to the third operating mode. The first processingvariable is the remaining whole blood volume needed to achieve thedesired platelet yield, or Vb_(rem) (in ml). The second processingvariable is the volume of whole blood that is needed to be processed toachieve the desired volume of red blood cells RBC_(Goal), or Vb_(RBC).

[0057] When Vb_(rem)=Vb_(RBC), the controller 18 switches from the firstoperating mode to the second operating mode. When Vb_(rem) becomes zero,the controller switches from the second operating mode to the thirdoperating mode.

[0058] A. Calculating Vb_(rem)

[0059] The utility function F2 relies upon the calculation of Yld by thefirst utility function F1 to derive the whole blood volume needed to beprocessed to achieve Yld_(Goal). During blood processing, the utilityfunction F2 continuously derives the additional processed volume neededto achieve the desired platelet yield Vb_(rem) (in ml) by dividing theremaining yield to be collected by the expected average platelet countover the remainder of the procedure, with corrections to reflect thecurrent operating efficiency η_(Plt).

[0060] In the illustrated embodiment, the utility function F2 derivesthis value using the following expression:${Vb}_{r\quad {em}} = \frac{200,000 \times ( {{Yld}_{Goal} - {Yld}_{{Curre}\quad n\quad t}} )}{\eta_{Plt} \times {ACDil} \times ( {{Plt}_{Current} + {Plt}_{Post}} )}$

[0061] where:

[0062] Yld_(Goal) is the desired platelet yield (k/μl),

[0063] Vb_(rem) is the additional processing volume (ml) needed toachieve Yld_(Goal).

[0064] Yld_(Current) is the current platelet yield (k/μl) calculated bythe utility function F1 based upon current processing values (as setforth in the Summary that follows).

[0065] η_(plt) is the present (instantaneous) platelet collectionefficiency, which can be calculated based upon current processing values(as set forth in the Summary that follows).

[0066] ACDil is an anticoagulant dilution factor (as set forth in theSummary that follows).

[0067] Plt_(Current) is the current (instantaneous) circulating donorplatelet count, calculated based upon current processing values (as setforth in the Summary that follows).

[0068] Plt_(post) is the expected donor platelet count after processing,also calculated based upon total processing values (as set forth in theSummary that follows).

[0069] B. Calculating Vb_(RBC)

[0070] The utility function F2 derives Vb_(RBC) based upon RBC_(Goal),and also by taking into account the donor's whole blood hematocrit(Hct). The donor's whole blood hematocrit Hct can comprise a valuemeasured at the outset of the procedure, or a value that is sensedon-line during the course of the procedure.

[0071] In the illustrated embodiment, Hct is not directly measured orsensed. Instead, the controller 18 relies upon an apparent hematocritvalue H_(b) of whole blood entering the separation chamber. H_(b) isderived by the controller 18 based upon sensed flow conditions andtheoretical consideration. The derivation of H_(b) is described in moredetail in the Summary that follows.

[0072] Based upon H_(b), the utility function F2 can derive Vb_(RBC)using the following expression:${Vb}_{RBC} = \frac{{RBC}_{Goal} + {Buf}}{H_{b}}$

[0073] where:

[0074] Buf is a prescribed buffer volume, e.g., 20 ml.

[0075] In the illustrated embodiment, the utility function F2 provides afurther volume buffer, by rounding up the calculated volume of Vb_(RBC),e.g., to the next highest integer divisible by ten.

[0076] In the illustrated embodiment, the utility function F2 alsocompares the calculated value of Vb_(RBC) to a prescribed maximum volume(e.g., 600 mL). If Vb_(RBC) equals or exceeds the prescribed maximum,the utility function F2 rounds the value down to a prescribed lesseramount, e.g., to 595 mL.

[0077] C. The First Operating Mode

[0078] In the first or non-concurrent operating mode, the system 10processes whole blood and collects PC and PPP for storage. During thefirst mode, RBC and the uncollected volume of PPP are returned to thedonor.

[0079] The system 10 shown in FIG. 1 employs one, single lumenphlebotomy needle 22. During the non-concurrent mode, the controller 18operates the system 10 in successive draw and return cycles. During thedraw cycle (FIG. 3), the controller 18 supplies the donor's WB throughthe needle 22 to the chamber 16 for processing. During the return cycle(FIG. 4), the controller 18 returns the RBC and PPP blood components tothe donor through the same needle 22.

[0080] In the illustrated embodiment, the system 10 is configured toenable separation to occur in the chamber 16 without interruption duringa succession of draw and return cycles. More particularly, the system 10includes a draw reservoir 66. During a draw cycle (FIG. 3), a quantityof the donor's WB is pooled in the reservoir 66, in excess of the volumewhich is sent to the chamber 16 for processing. The system 10 alsoincludes a return reservoir 68. A quantity of RBC collects in the returnreservoir 68 during the draw cycle for periodic return to the donorduring the return cycle (see FIG. 4). During the return cycle, WB isconveyed from the draw reservoir 66 to the chamber 16 to sustainuninterrupted separation.

[0081] In a draw cycle of the non-concurrent mode FIG. 3), the wholeblood pump Pi direct WB from the needle 22 through a first tubing branch20 and into the draw reservoir 66. Meanwhile, an auxiliary tubing branch26 meters anticoagulant from the container C1 to the WB flow through theanticoagulant pump P3. While the type of anticoagulant can vary, theillustrated embodiment uses ACDA, which is a commonly used anticoagulantfor pheresis.

[0082] A container C2 holds saline solution. Another auxiliary tubingbranch 28 conveys the saline into the first tubing branch 20, via the inline valve V1, for use in priming and purging air from the assembly 14before processing begins. Saline solution is also introduced again afterprocessing ends to flush residual components from the assembly 14 forreturn to the donor.

[0083] The processing controller 18 receives processing information froma weigh scale 70. The weigh scale 70 monitors the volume of WB collectedin the draw reservoir 66. Once the weigh scale 70 indicates that adesired volume of WB is present in the draw reservoir 66, the controller18 commands the whole blood processing pump P2 to operate tocontinuously convey WB from the draw reservoir 66 into the first stage24 of the processing chamber 16 through inlet branch 36. The controller18 operates the whole blood pump P1 at a higher flow rate (at, forexample, 100 ml/min) than the whole blood processing pump P2, whichoperates continuously (at, for example, 50 ml/min), so a volume ofanticoagulated blood collects in the reservoir 66. By monitoring weightusing the weigh scale 70, the controller intermittently operates thewhole blood inlet pump P1 to maintain a desired volume of WB in the drawreservoir 66.

[0084] Anticoagulated WB enters and fills the first stage 24 of theprocessing chamber 16. There, centrifugal forces generated duringrotation of the centrifuge 12 separate WB into red blood cells (RBC) andplatelet-rich plasma (PRP).

[0085] A PRP pump P4 operates to draw PRP from the first stage 24 of theprocessing chamber 16 into a second tubing branch 30 for transport tothe second stage 32 of the processing chamber 16. There, the PRP isseparated into platelet concentrate (PC) and platelet-poor plasma (PPP).

[0086] The controller 18 optically monitors the location of theinterface between RBC and PRP within the first stage 24 of theprocessing chamber 16. The controller 18 operates the PRP pump P4 tokeep the interface at a desired location within the first stage 24 ofthe processing chamber 24. This keeps a substantial portion of theleukocytes, which occupy the interface, from entering the flow of PRP.

[0087] Optionally, the PRP can also be conveyed through a filter F toremove leukocytes before separation in the second stage 32. The filter Fcan employ filter media containing fibers of the type disclosed inNishimura et al U.S. Pat. No. 4,936,998, which is incorporated herein byreference. Filter media containing these fibers are commercially sold byAsahi Medical Company in filters under the trade name SEPACELL.

[0088] The system 10 includes a recirculation tubing branch 34 and anassociated recirculation pump P5. The processing controller 18 operatesthe pump P5 to divert a portion of the PRP exiting the first stage 24 ofthe processing chamber 16 for remixing with the WB entering the firststage 24 of the processing chamber 16. The recirculation of PRPestablishes desired conditions in the entry region of the first stage 24to provide maximal separation of RBC and PRP.

[0089] A RBC branch 38 conveys the RBC from the first stage 24 of theprocessing chamber 16 to the return reservoir 68 (which is controlled byvalve V3). A weigh scale 72 monitors the volume of PPP collected in thecontainer C4.

[0090] A PPP branch 40 conveys PPP from the second stage 32 of theprocessing chamber 16, by operation of the PPP pump P7. By opening valveV5, all or a portion of the PPP can be directed to a collectioncontainer C4, depending upon the flow rate of the pump P7. A weigh scale74 monitors the volume of PPP collected in the container C4. The PPPthat is not collected flow into the return reservoir 68, where it mixeswith the RBC.

[0091] During the second operating mode (which will be described later),a relatively large volume of PPP (i.e., from about 50% to 75% ofPPP_(Goal)) will typically be collected without return to the donor. Inanticipation of this, the controller 16 limits the rate at which PPP iscollected during the first mode. This avoids the collection of a surplusvolume of PPP at the end of the procedure. By limiting the rate at whichPPP is collected during the first operating mode, the controller 18reduces the time of the subsequent blood volume trimming function,thereby reducing the overall procedure time. The small volume of surplusPPP also allows the use of higher return flow rates during the bloodvolume trimming function, as the amount of anticoagulant (carried in thePPP) that is returned to the donor during the blood volume trimmingfunction is reduced.

[0092] The controller 18 receives processing information from the weighscale 72, monitors the volume of RBC and PPP in the return reservoir 68.When a preselected volume exists, the controller 18 shifts the operationof the system 10 from a draw cycle to a return cycle.

[0093] In the return cycle (FIG. 4), the controller 18 stops the wholeblood inlet pump P1 and anticoagulant pump P3 and starts a blood returnpump P6. A return branch 42 conveys RBC and PPP in the return reservoir68 to the donor through the needle 22.

[0094] Meanwhile, while in the return cycle, the controller 18 keeps theWB processing pump P2, the PRP pump P4, and recirculation pump P5 inoperation to continuously process the WB pooled in the draw reservoir 66through the first stage and second stages 24 and 32 of the chamber 16.

[0095] When the weigh scale 72 indicates that the contents of the returnreservoir 68 have been conveyed to the donor, the controller 18 shiftsoperation of the system 10 to another draw cycle.

[0096] The controller 18 toggles between successive draw and returncycles until Vb_(rem)=Vb_(RBC). When Vb_(rem)=Vb_(RBC), the controller18 commands a final return cycle, to return the contents of the returnreservoir 68 to the donor. Upon returning the contents of the returnreservoir 68, the controller 18 switches from the first operating modeto the second operating mode.

[0097] D. Concurrent Collection Mode

[0098] In a second or concurrent collection mode (FIG. 5), thecontroller 18 conditions to system 10 to operate in a sustained drawcycle, to process whole blood and concurrently collect the targetedvolume of RBC, along with associated additional volumes of PC and PPP.During the concurrent collection mode, the controller 18 does not switchoperation of the system 10 to a return cycle. There is only onesustained draw cycle during the concurrent collection mode, and nocomponents are returned to the donor.

[0099] During the sustained draw cycle of concurrent collection mode,the controller 18 avoids the collection of a large surplus volume ofwhole blood in the draw reservoir 66. In the illustrated embodiment, thecontroller 18 achieves this objective by maintaining a smaller flow ratedifferential between the whole blood inlet pump P1 and the whole bloodprocessing pump P2, compared to the differential maintained during thedraw cycle of non-concurrent collection mode. For example, in theillustrated embodiment, the whole blood inlet pump P1 is operated at aminimal differential of, e.g., only 1 mL/min, above the whole bloodprocessing pump P2.

[0100] To further assure that only a slight buffer volume of whole bloodis maintained in the draw reservoir 66 during the sustained draw cycleof concurrent collection mode, the weight scale 70 toggles the wholeblood inlet pump P1 and anticoagulant pump P3 off whenever the sensedvolume of blood in the draw reservoir 66 exceeds a specified minimumbuffer amount , e.g., 5 g.

[0101] During the sustained draw cycle of concurrent collection mode,red blood cells are directed into a collection container C4, via thevalve V4, which is opened for this purpose (return valve V3 is closed,so no RBC collect in the return reservoir 68). A weigh scale 108monitors the weight of the collection container C4.

[0102] An associated volume of PC collects in the second stage 32 of thechamber 16, while the associated volume of PPP collects in thecollection container C3 (through the operation of the PPP pump P7 andvalve V5, which is opened). Valve V3 is closed , so no PPP collects inthe return reservoir 68.

[0103] The controller 18 continuously derives Vb_(rem) during thesustained draw cycle of concurrent collection mode. When Vb_(rem)becomes zero, the controller 18 terminates the concurrent collectionmode.

[0104] E. Blood Volume Trimming Function

[0105] In the illustrated embodiment (see FIG. 6), at the end of theconcurrent collection mode, the controller 18 assesses the volumes ofRBC and PPP that have been collected, using weigh scales 108 and 74,respectively.

[0106] If the volume of RBC collected exceeds RBC_(Goal), the controller18 commands the system 10 to enter a return cycle to return the excessRBC volume to the donor from the collection container C4, through thebranch path 43 (valve V6 being opened), and into the return path 42(valve V2 being closed), by operation of the in-line return pump P6.

[0107] Likewise, if the volume of PPP collected exceeds PPP_(Goal) thecontroller 18 commands the system 10 to enter a return cycle to returnthe excess PPP volume to the donor from the collection container C3,through the branch path 45 (valve V7 being opened and valve V5 beingclosed), and into the return path 42, by operation of the in-line returnpump P6.

[0108] At the end of the blood volume trimming function, the controller18 commands a saline reinfusion operation to return residual blood inthe system 10 to the donor, along with a prescribed fluid replacementvolume.

[0109] F. Post Collection Processing

[0110] 1. PPP

[0111] The retention of PPP can serve multiple purposes, both during andafter the component separation process.

[0112] The retention of PPP serves a therapeutic purpose duringprocessing. PPP contains most of the anticoagulant that is metered intoWB during the component separation process. By retaining a portion ofPPP instead of returning it all to the donor, the overall volume ofanticoagulant received by the donor during processing is reduced. Thisreduction is particularly significant when large blood volumes areprocessed. The retention of PPP during processing also keeps the donor'scirculating platelet count higher and more uniform during processing.

[0113] The system 10 can also derive processing benefits from theretained PPP. For example, the system 10 can, in an alternativerecirculation mode, recirculate a portion of the retained PPP, insteadof PRP, for mixing with WB entering the first compartment 24. Or, shouldWB flow be temporarily halted during processing, the system 10 can drawupon the retained volume of PPP as an anticoagulated “keep-open” fluidto keep fluid lines patent. In addition, at the end of the separationprocess, the system 10 can draw upon the retained volume of PPP as a“rinse-back” fluid, to resuspend and purge RBC from the first stagecompartment 24 for return to the donor through the return branch 42.

[0114] 2. PC

[0115] After the separation process, the system 10 also operates in aresuspension mode to draw upon a portion of the retained PPP toresuspend PC in the second stage 24 for transfer and storage in thecollection container(s) C5. Resuspension and transfer of PC to thecollection containers C5 can be accomplished manually or on line.

[0116] Preferable, the container(s) C5 intended to store the PC are madeof materials that, when compared to DEHP-plasticized polyvinyl chloridematerials, have greater gas permeability that is beneficial for plateletstorage. For example, polyolefin material (as disclosed in Gajewski etal U.S. Pat. No. 4,140,162), or a polyvinyl chloride materialplasticized with tri-2-ethylhexyl trimellitate (TEHTM) can be used.

[0117] G. RBC

[0118] In the illustrated embodiment (see FIG. 7), a disposablecollection set 76 is provided to process the RBC volume collected forstorage.

[0119] The set 76 includes a transfer path 78. The transfer path 78 hasa sealed free end 80 designed to be connected in a sterile fashion to asealed tube segment 82 on the RBC collection container C4 (see FIG. 7).Known sterile connection mechanisms (not shown) like that shown inSpencer U.S. Pat. No. 4,412,835 can be used for connecting the transferpath 78 to the tube segment 82. These mechanisms form a molten sealbetween tubing ends, which, once cooled, forms a sterile weld.

[0120] A first bag 84 communicates with the transfer path 78 through alength of sample tubing 86. The first bag 84 contains a red blood celladditive solution S, e.g., SAG-M or ADSOL® Solution (Baxter HealthcareCorporation). Following coupling of the collection set 76 to the RBCcollection container C4, a conventional in-line frangible cannula 106 inthe sample tubing 86 is opened, and the red blood cell additive solutionS is transferred from the first bag 84 into the collection container C4for mixing with the collected RBC volume. The mixture of additivesolution and RBC can then be transferred back into the first bag 84.

[0121] Residual air in the first bag 84 can be vented into an in-lineair venting chamber 88, which communicates with the transfer path 78. Atthe same time, an aliquot of the collected RBC volume present in thefirst bag 84 can be expressed into the sample tubing 86.

[0122] The tubing 86 preferably carries an identification code 90 whichis identical to a code 90 printed on or otherwise applied to the firstbag 84. The tubing 86 is then closed with a conventional snap-apartseal, and the first bag 84 is detached from the collection set 76 forstoring the RBC volume. The tubing 86 can be further sealed in segments,using conventional tube sealers, to isolate multiple samples of the RBCfor analysis and cross-matching.

[0123] The set 76 also includes a second bag 92, which communicates withthe transfer path 78 downstream of the first bag 84 through a branchpath 94. The branch path 94 includes an in-line filter 96. The in-linefilter 96 carries a filtration medium 98 that selectively removesleukocytes from red blood cells. The filter can comprise, e.g., a R-3000Red Blood Cell Filter (Asahi Medical)

[0124] The mixture of red blood cells and additive solution can betransferred from the collection bag C4 to the second bag 92 through thein-line filter 96, by-passing the first bag 84. In this way, the set 76provides red blood cells essentially free of leukocytes, suitable forlong term storage.

[0125] An air venting path 100 extends from the second bag 92 to thetransfer path 78, bypassing the in-line filter 96. By opening aconventional break-away cannula 106 in the path 100, residual air in thesecond bag 92 can be vented through the path 100 into the in-line airventing chamber 88. A one-way valve 104 in the path 100 allows air andliquid flow in the path 100 away from the bag 92, but not in theopposite direction.

[0126] At the same time, an aliquot of the collected RBC present in thesecond bag 92 can be expressed into the venting path 100. The ventingpath 100 carries an identification code 102 which is identical to a code102 printed on or otherwise applied to the second bag 92. The ventingpath 100 and branch path 94 can be closed with a conventional snap-apartseal, to allow detachment of the second bag 92 from the transfer path78. The path 100 can also be sealed in segments, to provide multiplesamples of the RBC for analysis and cross-matching.

[0127] The collection set 76 provides the flexibility to provide a redblood cell product suitable for long term storage, which is eithernon-leukocyte reduced or leukocyte reduced before storage.

IV. Estimating Post-Procedure Donor Blood Status

[0128] In addition to the information that the utility functions F1 toF4 provide before, during, and after a selected blood processingprocedure, the controller 18 can also include utility functions F5 andF6, which provide additional information before, during, or after theprocedure, estimating the effect of the selected procedure upon thedonor's blood volume and hematocrit. More particularly, additionalutility function F5 provides an estimation of the donor's net fluidvolume deficit as a result of the procedure, which will be called thePost-Intravascular Volume Deficit or Post-IVD. The additional utilityfunction F6 provides an estimation of the hematocrit of the donor'sblood after the procedure, which will be called the Post-Hematocrit. Theutility functions F5 and F6 can be performed after any selected bloodprocessing procedure, e.g., after a procedure that collects plateletswithout collecting red blood cells, or after a procedure that collectsboth platelets and red blood cells.

[0129] Post-IVD or Post-Hematocrit can be derived by the utilityfunctions F5 or F6 at the beginning of the selected procedure based uponthe operating parameters existing at that time. Post-IVD orPost-Hematocrit can be updated by the utility functions F5 or F6 at anytime during the selected procedure as operating parameters change or arechanged by the operator.

[0130] The controller 18 desirably displays the values of thePost-Intravascular Volume Deficit, or other expressions thereof, and thePost-Hematocrit on the interface 58. The information can also bepresented in printed form, e.g., for paper record filing, or in dataform for offloading, e.g., to a centralized donor database.

[0131] Access to this information before, during, or after the selectedprocedure aids the operator in assessing the effect of the procedure onthe donor's blood volume. This information allows a blood center toassess the effect of a given procedure upon the donor, so that a bloodcenter can optimize its collection of blood products from a donor,without compromising donor safety or regulatory requirements.

[0132] A. Utility Function F5: Deriving Post-Intravascular VolumeDeficit

[0133] The Post-Intravascular Volume Deficit (Post-IVD) is defined asthe total maximum blood volume that the intended procedure will removefrom the donor, minus replacement volume of fluids (TotVolReplaced)provided to the donor over the course of the procedure. Stateddifferently, the Post-Intravascular Volume Deficit (Post-IVD) is anassessment of the donor's net fluid volume deficit resulting from theprocedure.

[0134] To derive the Post-Intravascular Volume Deficit Post-IVD), theutility function F5 derives the donor's total blood volume (DonVol) atthe start of the procedure. DonVol is based upon the donor's gender,height, and weight. DonVol can be derived empirically, e.g., accordingto Equation (13) in the Summary below.

[0135] The utility function F5 also derives the total volume of bloodproducts to be removed from the donor during the procedure. Thiscomprises the sum of the desired PC yield to be collected (Yld_(Goal)),the desired RBC volume to be collected(RBC_(Goal)), and the desired PPPvolume to be collected (PPP_(Goal)). Of course, depending uponobjectives of the particular selected procedure, one or more of theseblood volumes may be zero, if that blood product is not targeted forcollection by the procedure. These targeted values are inputted by theoperator at the beginning of a given procedure, and can be modified bythe operator during the course of the procedure.

[0136] The utility function F5 also desirably accounts for other bloodlosses the donor will experience, due to, e.g., the residual red bloodcell volume of the blood processing system, any cycle volume (for singleneedle systems), or any other blood volumes (Res-Vol) that will not bereturned to the donor at the end of the procedure. In this respect, theutility function F5 conducts a “worst case” blood loss scenario, onethat goes beyond accounting for only the volume of blood productscollected, and one that also accounts for blood loss from other sources,to assess an actual total blood volume loss from all sources.

[0137] The sum of the blood product volumes and Res-Vol comprise thetotal blood volume loss that the donor will experience as a result ofthe procedure (TotVolRemoved), expressed as follows:

TotVolRemoved=(Yld_(Goal))+(RBC_(Goal))+(PPP_(Goal))+(Res-Vol)

[0138] The utility function F5 also derives the total volume ofreplacement fluid (TotVolReplaced) that will be returned to the donorduring the procedure. This includes the volume of saline given to thedonor at the beginning of the procedure due to saline prime, plus theestimated volume of anticoagulant ACD to be used during the procedure.The sum of these volumes comprise the total replacement fluid volume forthe procedure (TotVolReplaced).

[0139] To derive Post-Intravascular Volume Deficit (Post-IVD), theutility function F5 subtracts TotVolReplaced from TotVolRemoved,expressed as follows:

Post-IVD=TotVolRemoved−TotVolReplaced

[0140] Numeric information pertaining to Post-IVD is desirably expressedto the operator in one or more different formats, which relay theinformation in the context of, e.g., a blood center policy or aregulatory requirement. For example, Post Procedure Net Fluid DeficitInformation can express Post-IVD as the percentage of the donor's totalblood volume prior to the procedure (DonVol), that is:

Post Procedure Net Fluid Deficit Information (%)=Post-IVD/DonVol.

[0141] As another example, Post Procedure Net Fluid Deficit Informationcan express Post-IVD as a fraction of the donor's weight (Wgt) (in kg),that is:

Post Procedure Net Fluid Deficit Information (mL/kg)=Post-IVD/Wgt.

[0142] The controller 18 can include programming that compares Post-IVDor Post Procedure Net Fluid Deficit Information to prescribe standards.The controller 18 can produce a cautionary output based upon thecomparison, if the derived value is not consistent with the prescribedstandards.

[0143] B. Utility Function F6: Deriving Post-Hematocrit

[0144] The Post-Hematocrit is defined as an estimation of the donor'stotal red blood cell volume remaining after the intended proceduredivided by an estimation of the donor's total blood fluid volumeremaining after the intended procedure.

[0145] In deriving Post-Hematocrit, the utility function F6 relies uponthree estimated quantities: (i) the donor's red blood cell volumeexisting prior to the procedure (Pre-RBC-Vol), which is a function ofthe donor's blood hematocrit measured prior to the procedure (Pre-Hct);(ii) the donor's red blood cell volume remaining after the procedure(Post-RBC-Vol), which is a function of the desired RBC volume to becollected (RBC_(Goal)) and system residual red blood cell volume(Res-Vol) (also used by utility function F5 above); and (iii) thedonor's total blood volume after the procedure (Post-Tot-Vol), which isa function of donor's total blood volume existing prior to the procedure(DonVol) and the Post-Intravascular Volume Deficit (Post-IVD), asderived by utility function F5.

[0146] More particularly, to estimate Pre-RBC-Vol, an actual measurementof the donor's blood hematocrit (Pre-Hct) before the procedure ispreferably relied upon. The value of Pre-Hct is inputted to thecontroller 18 for processing by the utility function F6. Alternatively,an accurate estimation of the donor's blood hematocrit before theprocedure can be used as Pre-Hct. To derive Pre-RBC-Vol, the utilityfunction F6 multiplies the donor's total blood volume (DonVol) prior toprocedure (derived in the same manner as utility function F5) by thedonor's blood hematocrit prior to the procedure (Pre-Hct), expressed asfollows:

Pre-RBC-Vol=DonVol×Pre-Hct

[0147] To estimate Post-RBC-Vol, the utility function F6 subtracts thesum of the desired RBC volume to be collected (RBC_(Goal)) and thesystem residual blood volume (Res-Vol) (also used by utility function F5above) from the donor's pre-procedure red blood cell volume(Pre-RBC-Vol), expressed as follows:

Post-RBC-Vol=Pre-RBC-Vol−(RBC_(Goal)+Res-Vol)

[0148] To determine Post-Tot-Vol, the utility function F6 subtracts fromthe donor's total blood volume existing prior to the procedure (DonVol),the Post-Intravascular Volume Deficit (Post-IVD), as derived by utilityfunction F5, expressed as follows:

Post-Tot-Vol=DonVol−Post-IVD

[0149] To derive Post-Hematocrit, the utility function F6 divides theestimation of the donor's red blood cell volume existing after theprocedure (Post-RBC-Vol) by the estimation of the donor's total bloodvolume existing after the procedure (Post-Tot-Vol), expressed asfollows:

Post-Hematocrit=Post-RBC-Vol/Post-Tot-Vol

[0150] Information pertaining to Post-Hematocrit is desirably processedfor display to the operator, along with the information pertaining toPost-IVD. Such information can also be presented in printed form ordownloaded in electronic form for data storage and manipulation.

[0151] The controller 18 can include programming that comparesPost-Hematocrit to prescribe standards. The controller 18 can produce acautionary output based upon the comparison, if the derived value is notconsistent with the prescribed standards.

V. Summary of the Other Processing Utility Functions F1 to F4

[0152] A. Deriving Platelet Yield

[0153] The utility function F1 makes continuous calculations of theplatelet separation efficiency (η_(plt)) of the system 10. The utilityfunction F1 treats the platelet separation efficiency η_(ptl) as beingthe same as the ratio of plasma volume separated from the donor's wholeblood relative to the total plasma volume available in the whole blood.The utility function F1 thereby assumes that every platelet in theplasma volume separated from the donor's whole blood will be harvested.

[0154] The donor's hematocrit changes due to anticoagulant dilution andplasma depletion effects during processing, so the separation efficiencyη_(plt) does not remain at a constant value, but changes throughout theprocedure. The utility function F1 contends with these process-dependentchanges by monitoring yields incrementally. These yields, calledincremental cleared volumes (ΔClrVol), are calculated by multiplying thecurrent separation efficiency η_(plt) by the current incremental volumeof donor whole blood, diluted with anticoagulant, being processed, asfollows:

ΔClrVol=ACDil×η_(plt)×ΔVOL_(proc)  Eq (1)

[0155] where:

[0156] ΔVol_(proc) is the incremental whole blood volume beingprocessed, and

[0157] ACDil is an anticoagulant dilution factor for the incrementalwhole blood volume, computed as follows: $\begin{matrix}{{ACDil} = \frac{A\quad C}{{A\quad C} + 1}} & {{Eq}\quad (2)}\end{matrix}$

[0158] where:

[0159] AC is the selected ratio of whole blood volume to anticoagulantvolume (for example 10:1 or “10”). AC may comprise a fixed value duringthe processing period. Alternatively, AC may be varied in a stagedfashion according to prescribed criteria during the processing period.

[0160] For example, AC can be set at the outset of processing at alesser ratio for a set initial period of time, and then increased insteps after subsequent time periods; for example, AC can be set at 6:1for the first minute of processing, then raised to 8:1 for the next 2.5to 3 minutes; and finally raised to the processing level of 10:1.

[0161] The introduction of anticoagulant can also staged by monitoringthe inlet pressure of PRP entering the second processing stage 32. Forexample, AC can be set at 6:1 until the initial pressure (e.g. at 500mmHg) falls to a set threshold level (e.g., 200 mmHg to 300 mmHg). ACcan then be raised in steps up to the processing level of 10:1, whilemonitoring the pressure to assure it remains at the desired level.

[0162] The utility function F1 also makes continuous estimates of thedonor's current circulating platelet count (Plt_(Circ)), expressed interms of 1000 platelets per microliter (μl) of plasma volume (or k/μl).Like η_(plt), Plt_(Circ) will change during processing due to theeffects of dilution and depletion. The utility function F1 incrementallymonitors the platelet yield in increments, too, by multiplying eachincremental cleared plasma volume ΔClrVol (based upon an instantaneouscalculation of η_(plt)) by an instantaneous estimation of thecirculating platelet count Plt_(Cir). The product is an incrementalplatelet yield (Δyld), typically expressed as e^(n) platelets, wheree^(n)=0.5×10^(n) platelets (e¹¹=0.5×10¹¹ platelets).

[0163] At any given time, the sum of the incremental platelet yieldsΔYld constitutes the current platelet yield Yld_(Current), which canalso be expressed as follows: $\begin{matrix}{{Yld}_{{Curre}\quad n\quad t} = {{Yld}_{old} + \frac{\Delta \quad {ClrVol} \times {Plt}_{Cur}}{100,000}}} & {{Eq}\quad (3)}\end{matrix}$

[0164] where:

[0165] Yld_(Old) is the last calculated Yld_(Current), and$\begin{matrix}{{\Delta \quad {Yld}} = \frac{\Delta \quad {ClrVol} \times {Plt}_{Current}}{100,000}} & {{Eq}\quad (4)}\end{matrix}$

[0166] where:

[0167] Plt_(current) is the current (instantaneous) estimate of thecirculating platelet count of the donor.

[0168] ΔYld is divided by 100,000 in Eq (4) to balance units.

[0169] The following provides further details in the derivation of theabove-described processing variables by the utility function F1.

[0170] 1. Deriving Overall Separation Efficiency η_(plt)

[0171] The overall system efficiency η_(plt) is the product of theindividual efficiencies of the parts of the system, as expressed asfollows:

η_(plt)=η_(1stSep)×η_(2ndSep)×η_(Anc)  Eq (5)

[0172] where:

[0173] η_(1stSep) is the efficiency of the separation of PRP from WB inthe first separation stage.

[0174] η_(2ndSep) is the efficiency of separation PC from PRP in thesecond separation stage.

[0175] η_(Anc) is the product of the efficiencies of other ancillaryprocessing steps in the system.

[0176] a. First Stage Separation Efficiency η_(1stsep)

[0177] The utility function F1 derives η_(1stSep) continuously over thecourse of a procedure based upon measured and empirical processingvalues, using the following expression: $\begin{matrix}{\eta_{Sep} = \frac{Q_{p}}{( {1 - H_{b}} )Q_{b}}} & {{Eq}\quad (6)}\end{matrix}$

[0178] where:

[0179] Q_(b) is the measured whole blood flow rate (in ml/min).

[0180] Q_(p) is the measured PRP flow rate (in ml/min).

[0181] H_(b) is the apparent hematocrit of the anticoagulated wholeblood entering the first stage separation compartment. H_(b) is a valuederived by the utility based upon sensed flow conditions and theoreticalconsiderations. The utility function F1 therefore requires no on-linehematocrit sensor to measure actual WB hematocrit.

[0182] The utility function F1 derives H_(b) based upon the followingrelationship: $\begin{matrix}{H_{b} = \frac{H_{rbc}( {Q_{b} - Q_{p}} )}{Q_{b}}} & {{Eq}\quad (7)}\end{matrix}$

[0183] where:

[0184] H_(rbc) is the apparent hematocrit of the RBC bed within thefirst stage separation chamber, based upon sensed operating conditionsand the physical dimensions of the first stage separation chamber. Aswith H_(b), the utility function F1 requires no physical sensor todetermine H_(rbc), which is derived by the utility function according tothe following expression: $\begin{matrix}{H_{rbc} = {1 - ( {\frac{\beta}{g\quad A\quad \kappa \quad S_{\gamma}}( {q_{b} - q_{p}} )} )^{\frac{1}{k + 1}}}} & {{Eq}\quad (8)}\end{matrix}$

[0185] where:

[0186] q_(b) is inlet blood flow rate (cm³/sec), which is a knownquantity which, when converted to ml/min, corresponds with Q_(b) in Eq(6).

[0187] q_(p) is measured PRP flow rate (in cm³/sec), which is a knownquantity which, when converted to ml/min corresponds with Q_(p) in Eq(6).

[0188] β is a shear rate dependent term, and S_(γ)is the red blood cellsedimentation coefficient (sec). Based upon empirical data, Eq (8)assumes that β/S_(γ)=15.8×10⁶ sec¹ ⁻.

[0189] A is the area of the separation chamber (cm²), which is a knowndimension.

[0190] g is the centrifugal acceleration (cm/sec²), which is the radiusof the first separation chamber (a known dimension) multiplied by therate of rotation squared Ω² (rad/sec²) (another known quantity).

[0191] k is a viscosity constant=0.625, and K is a viscosity constantbased upon k and another viscosity constant α=4.5, where:$\begin{matrix}{\kappa = {{\frac{k + 2}{\alpha}\lbrack \frac{k + 2}{k + 1} \rbrack}^{k + 1} = 1.272}} & {{Eq}\quad (9)}\end{matrix}$

[0192] Eq (8) is derived from the relationships expressed in thefollowing Eq (10): $\begin{matrix}{{H_{rbc}( {1 - H_{rbc}} )}^{({k + 1})} = \frac{\beta \quad H_{b}q_{b}}{g\quad A\quad \kappa \quad S_{\gamma}}} & {{Eq}\quad (10)}\end{matrix}$

[0193] set forth in Brown, The Physics of Continuous Flow CentrifugalCell Separation, “Artificial Organs” 1989; 13(1):4-20)). Eq (8) solvesEq (10) for H_(rbc).

[0194] b. The Second Stage Separation Efficiency η_(2ndSep)

[0195] The utility function F1 also derives η_(2ndsep) continuously overthe course of a procedure based upon an algorithm, derived from computermodeling, that calculates what fraction of log-normally distributedplatelets will be collected in the second separation stage 32 as afunction of their size (mean platelet volume, or MPV), the flow rate(Q_(p)), area (A) of the separation stage 32, and centrifugalacceleration (g, which is the spin radius of the second stage multipliedby the rate of rotation squared Ω²).

[0196] The algorithm can be expressed in terms of a function, whichexpressed η_(2ndSep) in terms of a single dimensionless parametergAS_(p)/Q_(p),

[0197] where:

[0198] S_(p)=1.8×10⁻⁹ MPV^(2/3) (sec), and

[0199] MPV is the mean platelet volume (femtoliters, fl, or cubicmicrons), which can be measured by conventional techniques from a sampleof the donor's blood collected before processing. There can bevariations in MPV due to use of different counters. The utility functiontherefore may include a look up table to standardize MPV for use by thefunction according to the type of counter used. Alternatively, MPV canbe estimated based upon a function derived from statistical evaluationof clinical platelet precount Plt_(PRE) data, which the utility functioncan use. The inventor believes, based upon his evaluation of suchclinical data, that the MPV function can be expressed as:

MPV (f1)≈11.5−0.009Plt _(PRE) (k/μl)

[0200] c. Ancillary Separation Efficiencies η_(Anc)

[0201] η_(Anc) takes into account the efficiency (in terms of plateletloss) of other portions of the processing system. η_(Anc) takes intoaccount the efficiency of transporting platelets (in PRP) from the firststage chamber to the second stage chamber; the efficiency oftransporting platelets (also in PRP) through the leukocyte removalfilter; the efficiency of resuspension and transferral of platelets (inPC) from the second stage chamber after processing; and the efficiencyof reprocessing previously processed blood in either a single needle ora double needle configuration.

[0202] The efficiencies of these ancillary process steps can be assessedbased upon clinical data or estimated based upon computer modeling.Based upon these considerations, a predicted value for η_(Anc) can beassigned, which Eq (5) treats as constant over the course of a givenprocedure.

[0203] 2. Deriving Donor Platelet Count (Plt_(Circ))

[0204] The utility function F1 relies upon a kinetic model to predictthe donor's current circulating platelet count Plt_(Circ) duringprocessing. The model estimates the donor's blood volume, and thenestimates the effects of dilution and depletion during processing, toderive Plt_(Circ), according to the following relationships:

Plt _(Circ)=[(Dilution)×Plt _(Pre)]−(Depletion)  Eq (11)

[0205] where:

[0206] Plt_(Pre) is the donor's circulating platelet count beforeprocessing begins (k/μl), which can be measured by conventionaltechniques from a sample of whole blood taken from the donor beforeprocessing. There can be variations in Plt_(pre) due to use of differentcounters (see, e.g., Peoples et al., “A Multi-Site Study of VariablesAffecting Platelet Counting for Blood Component Quality Control,”Transfusion (Special Abstract Supplement, 47th Annual Meeting), v. 34,No. 10S, October 1994 Supplement). The utility function therefore mayinclude a look up table to standardize all platelet counts (such as,Plt_(Pre) and Pltpost, described later) for use by the functionaccording to the type of counter used.

[0207] Dilution is a factor that reduces the donor's preprocessingcirculating platelet count Plt_(Pre) due to increases in the donor'sapparent circulating blood volume caused by the priming volume of thesystem and the delivery of anticoagulant. Dilution also takes intoaccount the continuous removal of fluid from the vascular space by thekidneys during the procedure.

[0208] Depletion is a factor that takes into account the depletion ofthe donor's available circulating platelet pool by processing. Depletionalso takes into account the counter mobilization of the spleen inrestoring platelets into the circulating blood volume during processing.

[0209] a. Estimating Dilution

[0210] The utility function F1 estimates the dilution factor based uponthe following expression: $\begin{matrix}{{Dilution} = {1 - \frac{{Prime} + \frac{2\quad {ACD}}{3} - {PPP}}{DonVol}}} & {{Eq}\quad (12)}\end{matrix}$

[0211] where:

[0212] Prime is the priming volume of the system (ml).

[0213] ACD is the volume of anticoagulant used (current or end-point,depending upon the time the derivation is made)(ml).

[0214] PPP is the volume of PPP collected (current or goal) (ml).

[0215] DonVol (ml) is the donor's blood volume based upon models thattake into account the donor's height, weight, and sex. These models arefurther simplified using empirical data to plot blood volume againstdonor weight linearized through regression to the following, morestreamlined expression:

DonVol=1024+51Wgt(r ²=0.87)  Eq (13)

[0216] where:

[0217] Wgt is the donor's weight (kg).

[0218] b. Estimating Depletion

[0219] The continuous collection of platelets depletes the availablecirculating platelet pool. A first order model predicts that the donor'splatelet count is reduced by the platelet yield (Yld) (current or goal)divided by the donor's circulating blood volume (DonVol), expressed asfollows: $\begin{matrix}{{Dep1} = \frac{100,000{Yld}}{DonVol}} & {{Eq}\quad (14)}\end{matrix}$

[0220] where:

[0221] Yld is the current instantaneous or goal platelet yield (k/μl).In Eq (14), Yld is multiplied by 100,000 to balance units.

[0222] Eq (14) does not take into account splenic mobilization ofreplacement platelets, which is called the splenic mobilization factor(or Spleen). Spleen indicates that donors with low platelets countsnevertheless have a large platelet reserve held in the spleen. Duringprocessing, as circulating platelets are withdrawn from the donor'sblood, the spleen releases platelets it holds in reserve into the blood,thereby partially offsetting the drop in circulating platelets. Theinventor has discovered that, even though platelet precounts vary over awide range among donors, the total available platelet volume remainsremarkably constant among donors. An average apparent donor volume is3.10±0.25 ml of platelets per liter of blood. The coefficient ofvariation is 8.1%, only slightly higher than the coefficient ofvariation in hematocrit seen in normal donors.

[0223] The mobilization factor Spleen is derived from comparing actualmeasured depletion to Depl (Eq (14)), which is plotted and linearized asa function of Plt_(Pre). Spleen (which is restricted to a lower limitof 1) is set forth as follows:

Spleen=[2.25−0.004Plt _(Pre)]≧1  Eq (15)

[0224] Based upon Eqs (14) and (15), the utility function derivesDepletion as follows: $\begin{matrix}{{Depletion} = \frac{100,000{Yld}}{{Spleen} \times {DonVol}}} & {{Eq}\quad (16)}\end{matrix}$

[0225] 3. Real Time Procedure Modifications

[0226] The operator will not always have a current platelet pre-countPlt_(pre) for every donor at the beginning of the procedure. The utilityfunction F1 allows the system to launch under default parameters, orvalues from a previous procedure. The utility function F1 allows theactual platelet pre-count Plt_(Pre), to be entered by the operator laterduring the procedure. The utility function F1 recalculates plateletyields determined under one set of conditions to reflect the newlyentered values. The utility function F1 uses the current yield tocalculate an effective cleared volume and then uses that volume tocalculate the new current yield, preserving the platelet pre-countdependent nature of splenic mobilization.

[0227] The utility function F1 uses the current yield to calculate aneffective cleared volume as follows: $\begin{matrix}{{ClrVol} = \frac{100,000 \times {DonVol} \times {Yld}_{Current}}{\begin{matrix}{\lbrack {{DonVol} - {Prime} - \frac{ACD}{3} + \frac{PPP}{2}} \rbrack \times} \\{{Pre}_{Old} - \frac{50,000 \times {Yld}_{current}}{{Spleen}_{Old}}}\end{matrix}}} & {{Eq}\quad (17)}\end{matrix}$

[0228] where:

[0229] ClrVol is the cleared plasma volume.

[0230] DonVol is the donor's circulating blood volume, calculatedaccording to Eq (13).

[0231] Yld_(Current) is the current platelet yield calculated accordingto Eq (3) based upon current processing conditions.

[0232] Prime is the blood-side priming volume (ml).

[0233] ACD is the volume of anticoagulant used (ml).

[0234] PPP is the volume of platelet-poor plasma collected (ml).

[0235] Pre_(Old) is the donor's platelet count before processing enteredbefore processing begun (k/μl).

[0236] Spleen_(Old) is the splenic mobilization factor calculated usingEq (16) based upon Pre_(Old).

[0237] The utility function F1 uses ClrVol calculated using Eq (17) tocalculate the new current yield as follows: $\begin{matrix}{{Yld}_{New} = {\quad{\lbrack \frac{{DonVol} - {Prime} - \frac{ACD}{3} + \frac{PPP}{2}}{{DonVol}\frac{ClrVol}{2 \times {Spleen}_{New}}} \rbrack \times \lbrack \frac{{ClrVol} \times {Pre}_{New}}{100,000} \rbrack}}} & {{Eq}\quad (18)}\end{matrix}$

[0238] where:

[0239] Pre_(New) is the revised donor platelet pre-count entered duringprocessing (k/μl).

[0240] Yld_(New) is the new platelet yield that takes into account therevised donor platelet pre-count Pre_(New).

[0241] ClrVol is the cleared plasma volume, calculated according to Eq(17).

[0242] DonVol is the donor's circulating blood volume, calculatedaccording to Eq (13), same as in Eq (17).

[0243] Prime is the blood-side priming volume (ml), same as in Eq (17).

[0244] ACD is the volume of anticoagulant used (ml), same as in Eq (17).

[0245] PPP is the volume of platelet-poor plasma collected (ml), same asin Eq (17).

[0246] Spleen_(New) is the splenic mobilization factor calculated usingEq (15) based upon Pre_(New)

[0247] 4. Remaining Procedure Time

[0248] The utility function F2 can also calculate remaining collectiontime (t_(rem)) (in min) as follows: $\begin{matrix}{t_{{re}\quad m} = \frac{V\quad b_{{re}\quad m}}{Q_{b}}} & {{Eq}\quad (19)}\end{matrix}$

[0249] where:

[0250] Vb_(rem) is the remaining volume to be processed, calculatedusing Eq (19) based upon current processing conditions.

[0251] Qb is the whole blood flow rate, which is either set by the useror otherwise derived by the controller 18.

[0252] 5. Plasma Collection

[0253] The utility function F2 adds the various plasma collectionrequirements to derive the plasma collection volume (PPP_(Goal)) (in ml)as follows:

PPP _(Goal) =PPP _(PC) +PPP _(Source) +PPP _(Reinfuse) +PPP _(Waste)+PPP _(CollCham)  Eq (20)

[0254] where:

[0255] PPP_(PC) is the platelet-poor plasma volume selected for the PCproduct, which can have a typical default value of 250 ml, or beotherwise calculated by the controller 18 based upon current processingconditions.

[0256] PPP_(source) is the platelet-poor plasma volume selected forcollection as source plasma.

[0257] PPP_(Waste) is the platelet-poor plasma volume selected to beheld in reserve for various processing purposes (Default=30 ml).

[0258] PPP_(CollCham) is the volume of the plasma collection chamber(Default=40 ml).

[0259] PPP_(Reinfuse) is the platelet-poor plasma volume that will bereinfusion during processing.

[0260] 6. Plasma Collection Rate

[0261] The utility function F2 calculates the plasma collection rate(Q_(ppp)) (in ml/min) as follows: $\begin{matrix}{Q_{PPP} = \frac{{PPP}_{Goal} - {PPP}_{Current}}{t_{{re}\quad m}}} & {{Eq}\quad (21)}\end{matrix}$

[0262] where:

[0263] PPP_(Goal) is the desired platelet-poor plasma collection volume(ml).

[0264] PPP_(Current) is the current volume of platelet-poor plasmacollected (ml).

[0265] t_(rem) is the time remaining in collection, calculated using Eq(19) based upon current processing conditions.

[0266] 7. Total Anticipated AC Usage

[0267] The utility function F2 can also calculate the total volume ofanticoagulant expected to be used during processing (ACD_(End)) (in ml)as follows: $\begin{matrix}{{ACD}_{End} = {{ACD}_{Current} + \frac{Q_{b} \times t_{r\quad {em}}}{1 + {A\quad C}}}} & {{Eq}.\quad (22)}\end{matrix}$

[0268] where:

[0269] ACD_(Current) is the current volume of anticoagulant used (ml).

[0270] AC is the selected anticoagulant ratio,

[0271] Q_(b) is the whole blood flow rate, which is either set by theuser or otherwise calculated by the controller 18 based upon currentprocessing conditions.

[0272] t_(rem) is the time remaining in collection, calculated using Eq(19) based upon current processing conditions.

[0273] Various features of the inventions are set forth in the followingclaims.

We claim:
 1. A blood processing system comprising a blood processingcircuit including an element to separate blood drawn from a donor intoat least one targeted blood component and a container to collect avolume of the targeted blood component, a controller to convey bloodthrough the blood processing circuit to perform a desired bloodcollection procedure and including a processing function to derive anestimated effect of the procedure upon the donor in terms of a net bloodfluid volume loss, and an output to present the estimated effect to anoperator.